lobelane and dihydrotetrabenazine

lobelane has been researched along with dihydrotetrabenazine* in 2 studies

Other Studies

2 other study(ies) available for lobelane and dihydrotetrabenazine

Article	Year
Quinolyl analogues of norlobelane: novel potent inhibitors of [(3)H]dihydrotetrabenazine binding and [(3)H]dopamine uptake at the vesicular monoamine transporter-2. Bioorganic & medicinal chemistry letters, 2015, Jul-01, Volume: 25, Issue:13 We have previously shown that quinolyl moieties are attractive structural replacements for the phenyl groups in lobelane. These quinolyl analogues had improved water-solubility over lobelane and retained the potent vesicular monoamine transporter-2 (VMAT-2) inhibitory properties of the parent compound, with quinlobelane (4) exhibiting potent inhibition of uptake at VMAT-2 (Ki=51nM). However, the VMAT-2 inhibitory properties of quinolyl analogues of norlobelane, which is equipotent with lobeline as an inhibitor of [(3)H]dopamine (DA) uptake at VMAT-2, have not been reported. In the current communication, we describe the synthesis of some novel des-methyl quinolyl analogues of lobelane that exhibit greater affinity (Ki=178-647nM) for the dihydrotetrabenazine binding site located on VMAT-2 compared with lobelane (Ki=970nM), norlobelane (Ki=2310nM) and quinlobelane (Ki=2640nM). The most potent compounds, 14 and 15, also exhibited inhibition of [(3)H]DA uptake at VMAT-2 (Ki=42nM) which was comparable to both lobelane (Ki=45nM) and norlobelane (Ki=43nM). Results reveal that binding affinity at VMAT-2 serves as an accurate predictor of inhibition of the function of VMAT-2 for the majority of these analogues. These novel analogues are under consideration for further development as treatments for methamphetamine abuse. Topics: Amphetamine-Related Disorders; Animals; Binding Sites; Dopamine; Humans; In Vitro Techniques; Kinetics; Lobeline; Methamphetamine; Rats; Structure-Activity Relationship; Synaptic Vesicles; Tetrabenazine; Vesicular Monoamine Transport Proteins	2015
Pyrrolidine analogues of lobelane: relationship of affinity for the dihydrotetrabenazine binding site with function of the vesicular monoamine transporter 2 (VMAT2). Journal of medicinal chemistry, 2009, Dec-10, Volume: 52, Issue:23 Ring size reduction of the central piperidine ring of lobelane yielded pyrrolidine analogues that showed marked inconsistencies in their ability to bind to the dihydrotetrabenazine (DTBZ) binding site on the vesicular monoamine transporter-2 (VMAT2) and their ability to inhibit VMAT2 function. The structure-activity relationships indicate that structural modification within the pyrrolidine series resulted in analogues that interact with two different sites, i.e., the DTBZ binding site and an alternative site on VMAT2 to inhibit transporter function. Topics: Binding Sites; Lobeline; Protein Binding; Pyrrolidines; Structure-Activity Relationship; Tetrabenazine; Vesicular Monoamine Transport Proteins	2009

Article

Year

Quinolyl analogues of norlobelane: novel potent inhibitors of [(3)H]dihydrotetrabenazine binding and [(3)H]dopamine uptake at the vesicular monoamine transporter-2.

Bioorganic & medicinal chemistry letters, 2015, Jul-01, Volume: 25, Issue:13

We have previously shown that quinolyl moieties are attractive structural replacements for the phenyl groups in lobelane. These quinolyl analogues had improved water-solubility over lobelane and retained the potent vesicular monoamine transporter-2 (VMAT-2) inhibitory properties of the parent compound, with quinlobelane (4) exhibiting potent inhibition of uptake at VMAT-2 (Ki=51nM). However, the VMAT-2 inhibitory properties of quinolyl analogues of norlobelane, which is equipotent with lobeline as an inhibitor of [(3)H]dopamine (DA) uptake at VMAT-2, have not been reported. In the current communication, we describe the synthesis of some novel des-methyl quinolyl analogues of lobelane that exhibit greater affinity (Ki=178-647nM) for the dihydrotetrabenazine binding site located on VMAT-2 compared with lobelane (Ki=970nM), norlobelane (Ki=2310nM) and quinlobelane (Ki=2640nM). The most potent compounds, 14 and 15, also exhibited inhibition of [(3)H]DA uptake at VMAT-2 (Ki=42nM) which was comparable to both lobelane (Ki=45nM) and norlobelane (Ki=43nM). Results reveal that binding affinity at VMAT-2 serves as an accurate predictor of inhibition of the function of VMAT-2 for the majority of these analogues. These novel analogues are under consideration for further development as treatments for methamphetamine abuse.

Topics: Amphetamine-Related Disorders; Animals; Binding Sites; Dopamine; Humans; In Vitro Techniques; Kinetics; Lobeline; Methamphetamine; Rats; Structure-Activity Relationship; Synaptic Vesicles; Tetrabenazine; Vesicular Monoamine Transport Proteins

2015

Pyrrolidine analogues of lobelane: relationship of affinity for the dihydrotetrabenazine binding site with function of the vesicular monoamine transporter 2 (VMAT2).

Journal of medicinal chemistry, 2009, Dec-10, Volume: 52, Issue:23

Ring size reduction of the central piperidine ring of lobelane yielded pyrrolidine analogues that showed marked inconsistencies in their ability to bind to the dihydrotetrabenazine (DTBZ) binding site on the vesicular monoamine transporter-2 (VMAT2) and their ability to inhibit VMAT2 function. The structure-activity relationships indicate that structural modification within the pyrrolidine series resulted in analogues that interact with two different sites, i.e., the DTBZ binding site and an alternative site on VMAT2 to inhibit transporter function.

Topics: Binding Sites; Lobeline; Protein Binding; Pyrrolidines; Structure-Activity Relationship; Tetrabenazine; Vesicular Monoamine Transport Proteins

2009